N-halogenalkyl-c c-dialkylbarbituric acids and preparation of the same.



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UNITED STATES PATENT OFFICE.

or'ro worms. nAmas'rAn'r, GERMANY.

n-rIALoGENaLKYLo. o-n'uttxizimnnarruaro horns AND IBEPARATiON OF THE 7 I sans;

No Drawing.

To 'al l whom it may concern:

Be it known that I, Orro WoLrEs, a subject of the Emperor of Germany, and aresident of Darmstadt, in the Gizand Duchy of Hesse-Darmstadt, German Empire, have invented certain new'aiid' u'sefiil Improvements in N-Halogena'lkyl-G. G-Dialkylharbituric Acids and Preparation of the Same, of which the following is a, specification.

My invention relats broadly to a method for the preparation" of'N-halogenalkyl-C. C-dialkylbarbituric acids of the general type:

' X-N-CO (Xzhalogenalkyl, Yr hydro'gen or halogenallryl) and consists either in treating N alkylene G. O diallgylbarbituric acids with halogen, or with halogen-hydrids.

lhe N-halogenalkyl-G' G-dialkylbarbituric acids obtained by the method decribed below difier in a characteristic manner from the already known'hhallgyl-C. C-dialkylbarbituric acids (Ann/12m, 335,, 1904, page 349) The new compounds not only contain the residue of the dialkylbarbituric acids, which has become very valuable in modern medicine owing to its narcotic action, but also a halogen in the side chain which particularly in the case of the bromin derlvatives exhibits an important sedative action, which is characteristic of the organic bromin compounds. In this manner the new compounds incorporate the therapeutically highly valuable combination of two etiects and thus represent an important addition to'materia medioa.

My invention 'is'shown examples:

1. The condensation of monoallyl urea with diethylmalonic ester is, effected as inby the following dicated in German Patent No. 146,496 for other derivatives of urea. N-monoallyl-C. G diethylbarbituric acid crystallizes from dilute alcohol in colorless needles melting at about 77 C. The crystals are readily soluble in alcohol,'ether,'benz'ol, and dilute caustic allzalis. i

For the preparation of the bromin derivative 33 parts of N monoallyl-C. C-diethylmono N dibromo-propylbarbituric Spe o f Letters Patent Patented Sept. 16. 1 913. pplication m'ea December 13, 1e12- Serial No. 135,625.

barhiz uric acid ar dissolved in 4 pa s of glacial acetic acid with the aid of heat. The sqh tion isthen rapidly co le a a so tion oi 26 parts of bromi-n in 20 parts of glacial. ace ic. acid is ad e wi h s irring, Care being taken'to keep t e mixture cool. At first the halogen is quickly taken up, then more sl wl-y- Aft r. th mlxt re has e n allowed o stand at a temper re of 2 o 3 G. tor about one our, crys a zation is brought about by stirring. After standing for anbther hour the crystals are separated by the aid ofa centrifuge and covered with 50% alcohol. By recrystallization from hot alcohol, or by solution in hot toluol and precipitation by. petroleum ether, hI-dibro; mopropyl-C. .C-diethylbarbituric acid is obtained in colorless, small needles, melting at 124 C. (corr. 126).

2. A solution of 85 parts of bromin in 100 parts of glacial acetic acid is slowly added, with stirring, to a suspension of,174 parts of C. C dibenzyl N monoallylharbituric acid (prepared from dibenzyl malonic ester and monoallyl urea; melting point 130 C.) in 500 parts of glacial acetic acid, care being taken to keep the mixture cool. The solution is allowed to stand at a low temperature for'an'hour, protected from light, and is then poured into ice-water. The tough precipitate is'well treated with water several times, whereupon it is recrystallized from 9.0% alcohol with the addition of animal charcoal. The new product/ G. C-dibenzqylac1 crystallizes slowly 'in hard, small prisms, melting at 111 G. i The compound is readily soliible in hot alcohol, ether and benzol. It is' insolublein water. 3. '224 parts of C. C-diethyl-N-monoallylbarbituric acid are dissolved in 500 parts of lized from 90% alcohol, with the addition of animal charcoal. The compoundC.C-diethyl-N-dichloropropylbarbituric a,cidcorresponds to the following formula:

Cl-QH2.CH(CI).CH2.N co

l I Cally,

NH-CO Melting point 127 C. It is very readily soluble in chloroform, ether and alcohol. It also dissolves in dilute cold caustic soda solution without separation of halogen, and can be again precipitated by the addition of an acid.

4. 5 parts of C. C-diethyl-N-monoallylbarbituric acid are heated for one hour to 100 C. with 20 parts of glacial acetic acid, which have been previously saturated with hydrogen bromid. Crystallization sets in already on cooling. To completely separate the reaction product the solution is mixed with water. The precipitate is recrystallized from benzin or dilute alcohol. The productthen melts at 100 C. The compound is sparingly soluble in water, readily soluble in alcohol, ether and benzol. C. C-diethyl-N- monobromopropylbarbituric acid has probably the following composition:

5. 13.6 parts of C phenyl C ethyl N- monoallylbarbituric acid (prepared from phenylethylmalonic ester and monoallyl urea, crystals melting at 68 to 69 C., readily soluble in alcohol, ether, ethyl ace-v tate and benzol) are dissolved in 20 parts of glacial acetic acid and well cooled. A solution of 9 grams of bromin in 15. ams of glacial acetic acid is gradually added, with stirring; at the end of half an hour the solution is poured on to ice and the precipitate is carefully treated with ice-water. The product-C- phenyl- C- ethylmono-N --dibromo-propylbarbituric acidis then purified by recrystallization from dilute alcohol or methyl alcohol. It is readily soluble in alcohol, ether and benzol, it contains 37% of bromin, and corresponds to the formula C, H, O,N ,Br

6. ,NN-diallyl-C. C-d1ethylbarb1tur1c acid may also easily be brominated in the following manner: Asolution of 160 parts of bromin in 200 parts of benzol is gradually added, with stirring, to 130 parts of the 011 diluted with 200 parts of, benzol, care being taken to keep the mixture cool. The benzol is carefully removed by distillation, preferably under diminished pressure, the residue dissolved with the aid of heat in 500 parts of absolute alcohol and the solution cleared with animal charcoal. Oncooling, an oil first separates which slowly but completely assumes crystalline form. The NN-tetrabromodipropyl-C. C-diethylbarbituric acid thus obtained is carefully dried. It forms small, colorless prisms, melting at 64 C. On analysis it was found to contain 54:.770 of bromin, whereas for C H O N Br a content of 54.8% of bromin was calculated.

What I claim and desire to secure by Letters Patent is:

1. As a new product of. manufacture lflhalogenalkyl-C. C-dialkyl-barbituric acid containing the atom group 2. As a new product of manufacture mono- N-halogenalkyl-C. C-dialkyl-barbituric acid of the general formula:

I X-N-CO Alkyl 00 c Alkyl H- -co (X halogenalkyl) 3. As a new product of manufacture mono- N dihalogenalkyl C. C dialkylbarbituric acid of the general formula:

x-N-co A 1 do 0 my Eliss (X:dihalogenalkyl) barbituric acids withsubstances adding.

halogen.

7. The method of producing N-halogenalkyl-C. C-dialkylbarbituric acids and which consists in treating m0no-N-alkylene-C. C- dialkylbarbituric acids with substances adding halogen.

8. The method of producing mono-N- bromoalkyl-C. C-dialkylbarbituric acids and which consists in treating mono-N-alkylene- C. C-dialkylbarbituric acids with substances adding bromin.

9. The method of producing mono-N- dibromopropyl-C. C-dialkylbarbituric acids In testimony whereof I have hereunto and which consists in treatmg mono-N-allylsigned my name in the presence of the two 10 G. C-dialkylbairbituric acid with bromin. subscribing witnesses.

10. The method of producing mono-N-di- 5 bromopropylc. e diethylbarbituric acid OTTO WOLFES- and which consists in treating mono-N-allyl- Witnesses: C. G-diethylbarbituric acid with 2 atoms of JEAN GRUND,

bromin. CARL GRUND. 

